title: Age-dependent changes in the expression of regulatory cell surface ligands in activated human T-cells.
abstract: BACKGROUND
  The immune system consists of multiple preformed and more specific adaptive immune responses, which are all subject to both positive and negative regulation. Programmed cell death protein 1 (PD-1) is a cell surface ligand implicated in the induction of anergy, Inducible T-cell Costimulator (ICOS) plays a stimulatory role in the development of both CD4+ and CD8+ T-cells, Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) plays a role in inhibitory regulation of T-cell activity, and T cell immunoglobulin and mucin protein 3 (Tim-3) has been described as a negative regulatory molecule in CD4+ helper type 1 cells and CD8+ cytotoxic type 1 cells. Each of these ligands is induced with T-cell activation allowing greater opportunity to have a regulatory role.
  
  
  RESULTS
  Flow cytometry was used to quantitate the expression of PD-1, ICOS, CTLA-4 and Tim-3 in human T-cells from geriatric and younger subjects both at baseline and after in vitro induction by mitogen. The magnitude of expression of the molecules increased significantly on activated blasts after mitogen stimulation compared to their baseline levels in resting cells. The increase in CTLA-4 expressing CD8+ T-cells was significantly higher after in vitro induction in older persons, while the increase in cells expressing Tim-3 and PD-1 was significantly reduced. In CD4+ T-cells, a greater increase in CTLA-4 expressing cells in older persons was the only difference between the age groups.
  
  
  CONCLUSIONS
  We found several significant changes in the older individuals in regulatory elements of the adaptive immune system that occur particularly after immune activation. These differences could have ramifications to autoimmunity as well as immunology against infection and tumors.
authors.affiliation: Geriatric Research Center Clinical Center (GRECC), Louis Stokes Cleveland VA, 10701 East Blvd,, 44106 Cleveland, OH, USA. david.canaday@case.edu.
authors.forename: David H
authors.initials: DH
authors.lastname: Canaday
authors.forename: Karen E
authors.initials: KE
authors.lastname: Parker
authors.forename: Htin
authors.initials: H
authors.lastname: Aung
authors.forename: Hui Emily
authors.initials: HE
authors.lastname: Chen
authors.forename: Dariana
authors.initials: D
authors.lastname: Nunez-Medina
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Burant
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D008565:Membrane Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor